Selective Serotonin Reuptake Inhibitor Overdose

Selective serotonin reuptake inhibitors (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine) have a wide margin of safety in overdose, and deaths from a single agent are uncommon. Most patients have mild central nervous system symptoms. The significant exceptions are citalopram and escitalopram, which prolong the QT interval in a dose-dependent way and cause seizures, and combined ingestion with other serotonergic or cardiotoxic drugs.

Thresholds: ingestion of over 600 mg of citalopram (over 300 mg of escitalopram) carries a risk of seizure and torsades de pointes, and ECG monitoring is advised from 400 mg of citalopram or 200 mg of escitalopram. Sertraline above about 2.5 g and fluoxetine above 1.5 g produce seizures in some patients. Fluoxetine and its metabolite have long half-lives (2 to 9 days), so symptoms persist.

Complications: serotonin toxicity, seizures, torsades de pointes, hyponatremia from inappropriate antidiuretic hormone release, and rarely rhabdomyolysis.

• Nausea, vomiting, drowsiness, tremor, sinus tachycardia, mydriasis and dizziness
• Serotonin toxicity: agitation, diaphoresis, hyperreflexia, inducible or spontaneous clonus, hypertonia, fever
• Seizures (usually in the first 6 hours) and rarely coma
• Citalopram and escitalopram: QTc prolongation, bradycardia and ventricular arrhythmia, sometimes delayed for up to 12 hours
• Red flags: seizures, QTc over 500 ms, hyperthermia over 38.5 degrees Celsius, rigidity and coingestants

1. 12-lead ECG at presentation and repeated at 4 and 8 hours for citalopram and escitalopram, measuring QTc and QRS.
2. Blood tests: glucose, sodium (hyponatremia), potassium, magnesium, calcium, creatinine, creatine kinase.
3. Paracetamol and salicylate levels in every intentional ingestion.
4. Observation for at least 6 hours for most agents. Keep patients with citalopram or escitalopram on monitoring for 12 hours if the ingested dose is over the thresholds above.
5. Classify serotonin toxicity by examination for inducible clonus, ocular clonus, hyperreflexia, tremor, hypertonia and temperature.

Differentials: other serotonergic toxicity, anticholinergic poisoning, sympathomimetic toxicity, neuroleptic malignant syndrome, withdrawal syndromes.

1. Gut decontamination: activated charcoal 50 g orally (children 1 g/kg, maximum 50 g) within 1 hour if the airway is protected.
2. Supportive care: IV crystalloid, cardiac monitoring, correction of potassium to above 4.0 mmol/L and magnesium to above 0.8 mmol/L.
3. Seizures: lorazepam 4 mg IV (children 0.1 mg/kg, maximum 4 mg) or diazepam 10 mg IV (children 0.2 mg/kg), repeated once. Use midazolam 10 mg IM if no access.
4. QT prolongation: magnesium sulfate 2 g IV over 10 to 20 minutes, even when magnesium is normal. Torsades de pointes: magnesium 2 g IV bolus, then overdrive pacing at 100 to 120 beats a minute or isoprenaline 2 to 10 micrograms/min IV. Avoid class Ia, Ic and III antiarrhythmics, and other QT-prolonging drugs (ondansetron, haloperidol, macrolides).
5. Moderate serotonin toxicity: diazepam 5 to 10 mg IV every 5 to 10 minutes as needed, and cyproheptadine 12 mg orally (or by nasogastric tube) as a first dose, then 2 mg every 2 hours until symptoms settle, maintenance 8 mg every 6 hours (maximum 32 mg a day).
6. Severe toxicity (temperature over 41 degrees Celsius, rigidity): sedation, intubation and neuromuscular paralysis with rocuronium 1 mg/kg IV. Avoid succinylcholine. Active external cooling. Antipyretics are ineffective.
7. Hyponatremia: fluid restriction to 800 mL daily when sodium is below 130 mmol/L, and 3% saline 100 mL IV over 10 minutes only for seizures or severe symptoms (maximum correction 8 mmol/L in 24 hours).
8. Avoid physical restraint, which worsens hyperthermia and rhabdomyolysis.

Follow-up: psychiatric review before discharge, review of the antidepressant plan, and restriction of access to large quantities. Counsel on withdrawal if the drug is stopped abruptly after prolonged use.